Abstract
Activated pancreatic stellate cells (PSCs) play a pivotal role in the pathogenesis of pancreatic fibrosis and inflammation. Inhibition of activation and cell functions of PSCs is a potential target for the treatment of pancreatic fibrosis and inflammation. The polyphenol compound curcumin is the yellow pigment in curry, and has anti‐inflammatory and anti‐fibrotic properties. We here evaluated the effects of curcumin on the activation and cell functions of PSCs. PSCs were isolated from rat pancreas tissue and used in their culture‐activated, myofibroblast‐like phenotype unless otherwise stated. The effects of curcumin on proliferation, α‐smooth muscle actin gene expression, monocyte chemoattractant protein (MCP)‐1 production, and collagen expression were examined. The effect of curcumin on the activation of freshly isolated cells in culture was also assessed. Curcumin inhibited platelet‐derived growth factor (PDGF)‐induced proliferation, α‐smooth muscle actin gene expression, interleukin‐1β‐ and tumor necrosis factor (TNF)‐α‐induced MCP‐1 production, type I collagen production, and expression of type I and type III collagen genes. Curcumin inhibited PDGF‐BB‐induced cyclin D1 expression and activation of extracellular signal‐regulated kinase (ERK). Curcumin inhibited interleukin‐1β‐ and TNF‐α‐induced activation of activator protein‐1 (AP‐1) and mitogen‐activated protein (MAP) kinases (ERK, c‐Jun N‐terminal kinase (JNK), and p38 MAP kinase), but not of nuclear factor‐κB (NF‐κB). In addition, curcumin inhibited transformation of freshly isolated cells to myofibroblast‐like phenotype. In conclusion, curcumin inhibited key cell functions and activation of PSCs. J. Cell. Biochem. 97: 1080–1093, 2006. © 2005 Wiley‐Liss, Inc.